Victims of stroke most commonly die from cardiac causes. Although they have a high incidence of ischemic heart disease, autopsy and experimental studies in acute stroke indicate that cardiac ischemia is not the cause of death. Instead, increased sympathetic tone causing cardiac damage and arrhythmias is implicated. As a result of previous studies it is suggested that left middle cerebral artery (MCA) stroke involving the insula or right MCA stroke sparing the insula shifts cardiac autonomic balance towards sympathetic predominance which can cause cardiac arrhythmias. No prospective clinical studies have yet compared stroke location and cardiac outcome. Our overall goal is to reduce the prime cause of stroke-related mortality by determining whether cardiac outcomes after acute stroke differ according to: stroke location (AIM 1); in relation to cardiac autonomic tone (AIM 2); and whether patients at longterm risk for adverse cardiac outcome can be predicted by clinical neurological, cardiac and autonomic status using multivariate analysis (AIM3). The overall study design involves selection of patients within 1 week of hemisphere or brainstem stroke. Daily cardiac and neurological examinations will be performed for a further week. Pre-existing coronary artery disease (CAD) will be ascertained by examination, history, ECG, thallium scan and echocardiography; contribution of CAD to cardiac outcome will be treated by multivariate analysis. Cardiac outcomes include: new onset ECG changes, cardiac arrhythmias and changes in cardiac contractility and cardiac enzymes; myocardial infarction, angina and sudden cardiac death. These will be assessed during the first week after inclusion in the study and regularly for 1 year thereafter. Incidence of cardiac events will be related to stroke location and cardiac autonomic tone, and compared to the incidence in TIA patients as a control group. Cardiovascular autonomic tone will be assessed by spectral analysis of heart rate and blood pressure variability using a specially designed cardiac autonomic platform and by urinary catecholamine excretion. Control groups for comparison will include TIA patients and age-matched normal individuals. Accomplishment of these aims should indicate prevention strategies for the most common cause of post-stroke death.